Lecture 3-3: Principles and Molecules of Transmembrane Transport

Principles & Molecules of Transmembrane Transport

• Overview of membrane transport focusing on gut barrier function by Fredrik Jutfelt.

Selectivity of Transport Proteins

• Transport Proteins: Key facilitators that grant selectivity to lipid bilayers.

• Two Types of Membranes:

  • (A) Protein-free artificial lipid bilayer (liposome)

  • (B) Cell membrane

Movement Across Membranes

• Movement of atoms/molecules depends on:

• Concentration and properties of the molecules

• The hydrophobic layer of membranes acts as a barrier for some molecules

• Larger and polar molecules face challenges while smaller, non-polar ones face fewer obstacles

• Ions cannot penetrate the membrane

• A gradient in solute concentration across membranes drives solute movement

Channels and Transporters

• Types of Proteins for Solute Movement:

• Channels:

  • Create continuous open paths allowing rapid solute flow

  • Regulated states (open and closed) based on conditions (ligand, voltage, mechanically-gated)

  • Enable solute movement along concentration gradient (passive transport/facilitated diffusion)

• Transporters:

  • Move fixed amounts of solutes with conformational changes (slower than channels)

  • Some utilize facilitated diffusion; others engage in active transport (against concentration gradient)

• Selectivity: Both channels and transporters selectively move specific solutes.

Modes of Trans-Membrane Movement

• Simple Diffusion and Passive Transport: Solute movement with concentration gradient

• Active Transport: Movement against concentration gradient

• Different molecules can take distinct routes across membranes

Ion Movement and Membrane Voltage

• Ions Governed By:

• Chemical and electrical gradients influencing movement

• Opposite charges result in membrane voltage

• Cytosol and Extracellular Fluid: Electrically neutral; voltage exists at the membrane

• Movement driven by charge distribution and concentration gradients

• • charges are attracted to the negative inner leaflet, while + charges inside are repelled by the outer leaflet's positive charge

Aquaporin Channels

• Water diffuses through specific channels called Aquaporins

• Initial belief in free water passage; rapid transport necessitates dedicated channels

• Aquaporins facilitate water movement; findings illustrated by frog egg experiments in hypotonic solutions

• Osmosis dictates water movement based on solute concentrations

Management of Internal Water Pressure

• Cells of different organisms use unique strategies

• Solutes in contractile vacuoles draw water in

• Plant cells withstand high internal pressures due to cell walls

• Animal cells export solutes to reduce osmotic water influx

Cellular Membrane Transport Proteins

• Each type of cellular membrane possesses specialized transport proteins necessary for various solutes:

• Nucleotide, H+, sugar, amino acids, pyruvate, ATP, ADP, Na+, K+.

Passive Transporters Dynamics

• Function independent of solute binding through conformational changes

• A passive transporter's alternate conformations allow bidirectional solute movement

• Glucose transporters can facilitate increased inward movement based on concentration differences

Energy-Dependent Pumps

• Pumps: Utilize energy to move solutes against gradients

• Types include:

• Gradient-Driven Pumps: Use movement of one solute with its gradient to drive another solute against its gradient

• ATP-Driven Pumps: Harness ATP hydrolysis for movements

• Light-Driven Pumps: Convert light energy for conformational changes (e.g., bacteriorhodopsin)

Sodium-Potassium Pumps

• ATP Usage: Maintains Na+ and K+ gradients

• Key for maintaining reciprocal intracellular and extracellular concentrations

• Important for neuron function

Conformational Change in Na+-K+ Pump

• Process involves:

• Binding of Na+

• Pump phosphoylation by ATP

• Conformational change; Na+ ejected

• K+ binding and return to original state

Transporters by Number and Direction

• Symport: Two solutes in the same direction

• Antiport: Two solutes in opposite directions

• Uniport: One solute only

Potential Energy of Na+ Gradient

• Analogous to water behind a dam, offering potential energy for movement

Sodium-Glucose Symporters

• Facilitate glucose uptake in intestinal cells post-meal

• Passive transporters would prevent glucose accumulation; thus, it's coupled with sodium inflow

• Na+ gradient maintained by ATP-powered sodium pump supports nutrient uptake

Domain-Restricted Transporters

• Glucose Transport in Gut:

• Active sodium-glucose symporter moves glucose into absorptive cells

• Tight junctions prevent lateral diffusion, ensuring targeted transport

• Passive glucose transporters assist in moving glucose to extracellular fluid

• Na+-K+ pump prevents cytosolic sodium accumulation

• Similar mechanisms apply to amino acid transport

• Distinction: Animals preferentially use sodium gradients, while plants use proton gradients

Key Concepts

• Membranes act as diffusion barriers; larger, polar molecules struggle to cross

• Transport proteins regulate solute movement

• Channels provide rapid diffusion; transporters operate via conformational changes

• Passive transporters operate along gradients; pumps counter gradients through energy usage

• Ions influenced by combined chemical and electrical gradients

• Symporters and antiporters transport multiple solutes in designated directions

• Sodium gradient facilitates nutrient uptake; proton gradients favored in plants.